A. Sixty-six tumor cell lines from small cell-lung cancer patients have been studied for myc family DNA amplification. Fifteen of 35 (43%) cell lines established from previously treated small cell lung cancer patients have been amplified for one of the myc family genes compared to 3/30 (10%) of cell lines established from untreated patients. Chemotherapy treated small cell lung cancer patients whose tumor cell lines have c-myc family DNA amplification live a median of 27 weeks compared to 49 weeks for patients whose tumor cell lines do not have c-myc family DNA amplification. Thirty-eight tumors harvested from small cell lung cancer patients have been studied for myc family DNA amplification. Six of 38 (16%) have DNA amplification of one of the myc family of oncogenes (4 N-myc and 2 L-myc). All these were obtained from chemotherapy treated small cell lung cancer patients. myc family DNA amplification appears to be more common in chemotherapy treated small cell cancer patients and c-myc family DNA amplification is associated with shortened survival. B. Restriction fragment length polymorphism (RFLP) studies have shown that 33 of 35 patients with small cell lung cancer lose heterozygosity in the tumor tissue DNA that was present in normal tissue DNA. This confirms the loss of genetic information localized to the short arm of chromosome 3 previously described by karyotype analysis. Extrapulmonary small cell cancers have been studied using karyotype and RFLP analysis and 4/5 patients retain both chromosome 3's in the region of 3p14-21 by both RFLP analysis and karyotype analysis. This demonstrates a different genetic lesion in tumors that histologically are indistinguishable.